tbuckley/cabot-search huggingface dataset:
Additional prognostic value of the BCT score in patients with ER+HER2- breast cancer receiving 21-gene assay–guided adjuvant treatments.
Authors: Sung Gwe Ahn, Yoonwon Kook, Sae Byul Lee, Eun-Gyeong Lee, Jonghan Yu, Young-Won Lee, Yeon Jin Kim, Sang Uk Woo
Journal: Journal of Clinical Oncology (2023)

548 Background: In early estrogen receptor (ER)+HER2- breast cancer, a 21-gene expression assay-guided decision-making for adjuvant treatments has been widely utilized as a standard-of-care. The GenesWell BCT is a multigene assay that is designed to predict the risk of distant recurrence (DR) in patients with ER+HER2- breast cancer. This assay consists of nine genes, which are used to generate a risk score that can help guide treatment decisions. We addressed an additional value of the GenesWell Breast Cancer Test (BCT) score using the cohort of ER+HER2- breast cancer patients receiving a 21-gene assay-guided adjuvant treatments, focusing the chemotherapy untreated subset with low 21-gene recurrence score (RS). Methods: This multicentre, observational follow-up study was done in 4 academic institutions in South Korea. Patients with ER+HER2- breast cancer who received RS-guided adjuvant treatments were enrolled. A total of 705 patients were included. Of these, the rate of women with node-positive disease was 21.6% (152/705), and the rate of women with younger than 50 years old was 61.4% (433/705). The BCT score was obtained using the specimens which were previously analyzed for RS. The primary endpoint was recurrence-free survival (RFS), and the secondary endpoint was distant recurrence-free survival (DRFS). Results: Among the 705 patients, the RS assigned 110 (15.6%) as high risk (≥26), whereas the BCT score assigned 239 (33.9%) as high risk (≥4). The agreement between two tests was noted in 494 (70.1%); concordances were made in 69 for high and in 425 for low, respectively. At a median follow up of 85 months, 80 had tumor recurrences, 38 had distant recurrences, and the 7-year RFS was 90.0% (95% CI, 87.6%-92.5%). In the 595 patients with low RS, 556 (93.4%) did not receive adjuvant chemotherapy. Within the 556 chemotherapy-untreated patients with low RS, the RFS differed significantly according to the BCT score ( p= .014); the 7-year RFS was 92.9% in the BCT-low, while it was 85.7% in the BCT-high. Within the group, the BCT score was demonstrated as an independent prognostic factor for both RFS and DRFS adjustment of tumor size, nodal stage, and histologic grade. In addition, the RFS of the low-BCT score group was superior to that of the high-BCT group in either women younger than 50 years of age with an RS of 21 to 25 or all women with an RS of 21 to 25. Conclusions: We found that the BCT score was useful in stratifying the risk of relapse in chemotherapy-untreated patients with a low recurrence score (RS). This indicates that the BCT score could provide additional clinical value in identifying patients with a long-term risk of relapse, particularly in young women with an RS of 21 to 25.
Recent analysis of frequency of surrogate end points used in oncology clinical trials 2006-2022.
Authors: Akshit Chitkara, Manoj P. Rai, Rajat Thawani, Emerson Yu-sheng Chen
Journal: Journal of Clinical Oncology (2023)

e13658 Background: Surrogate endpoints expedite the clinical trial results at the cost of more uncertainty with clinical efficacy, as they may have a weak correlation with definite endpoints like overall survival (OS). Increased use of surrogate measures such as progression-free survival (PFS) and response rate (RR) are increasingly used by the FDA for drug registration trials in oncology. We conducted this analysis to update our previous analysis (2006-2017) and to study the recent trends in using these surrogate endpoints for approval by FDA. We also study how these surrogate markers are used across various therapy lines. Methods: Our retrospective analysis of US FDA oncology approvals from 2006 to 2022 examined FDA documents from the FDA website, package inserts, and related published trials. Only drug approvals for non-hematologic solid tumors were included. We collected data about the approval type, conversion to regular approval, drug withdrawals (until February 11, 2022), lines of therapy (first-line, second-line, and third or other lines), and endpoints used for FDA approval. All surrogate endpoints were categorized into response rate (RR), generally a proportion, or progression-free survival (PFS), a time-to-event endpoint. Definite endpoints, including patient-reported outcomes (PRO), were all included within the OS category. Results: We identified that OS/PRO endpoints accounted for only 29% (98 of 342) of drug indication approvals. In contrast, 71% of drug approvals (244 of 342) were based on surrogate endpoints; 37% (127 of 342) of drug indications used RR endpoints, followed by 34% (117 of 342) drug indications that used PFS endpoints. These surrogate endpoints (RR, PFS, CR, DFS, EFS, pCR, iDFS, MCR, MFS, ORR, RFS, rPFS combined) showed a trend toward being used in the third- or later-line line setting followed by second-line (91 of 145 drug indications [63%] for first-line vs. 102 of 138 drug indications [74%] for second-line vs. 38 of 43 drug indications [88%] for third- or later-line). Still, they were used in all lines of therapy. Conclusions: FDA commonly accepts surrogate endpoints as criteria for drug approval in oncology since 2006. There has been a trend toward using surrogate endpoints in the third or later lines of drug approvals by the FDA. There is a tradeoff between providing access to cancer therapies and potentially approving therapies that still have unverified clinical benefits.
Influence of adherence to adjuvant endocrine therapy in early breast cancer: Results from a large German real-world claims data analysis.
Authors: Dominik Dannehl, Tobias Engler, Tjeerd Dijkstra, Raphael Gutsfeld, Alexandra von Au, Markus Hahn, Sabine Hawighorst-Knapstein, Ariane Chaudhuri, Markus Wallwiener, Armin Bauer, Sara Brucker, Stephanie Wallwiener, Andreas Daniel Hartkopf
Journal: Journal of Clinical Oncology (2023)

551 Background: In hormone-receptor positive (HR+) early breast cancer (EBC) adjuvant endocrine therapy (ET) significantly reduces recurrence and mortality. The most common way to estimate therapy adherence is the use of patient reported outcome measures. Yet, this method is inaccurate due to the social-desirability bias. We therefore aimed to analyze adherence to ET over the first 5 years of treatment by using claims data from a large German health insurance provider (AOK Baden-Wuerttemberg). Methods: Female patients diagnosed with HR+ EBC between July 1 st 2010 and December 31 st 2019 were included into the analysis. Adherence to ET was defined as the ratio of the summed number of pills of filled prescriptions for ET (either aromatase inhibitors or tamoxifen) and the duration of endocrine therapy in days (from the start of the first prescription after completion of surgery and chemotherapy, if applicable). ET administration was observed over 5 years. High/low adherence was defined as a ratio between 0.8 – 1 and 0 – 0.8, respectively. ET duration was divided into yearly intervals and adherence was calculated as above. Continuous high/low adherence was then defined as an adherence between 0.8 – 1 and 0 – 0.8 in each year. Distant recurrence-free survival (DRFS) was calculated from the day of the first diagnosis of EBC until onset of distant metastatic disease. Overall survival (OS) was defined as the period between first diagnosis of EBC until death. Results: In total, 20998 patients were included. 17006 patients (81%) were HR+. Regarding overall adherence during the first 5 years, average adherence was 0.81 ± 0.26, with 72% of all HR+ patients showing high adherence to ET. Of 17006 HR+ EBC patients, 8363 (49%) showed a continuous high adherence to ET and 1731 (10%) showed a continuous low adherence to ET over 5 consecutive years. Continuous adherence to endocrine therapy had a significant impact on DRFS (HR: 0.61; 95% CI: 0.52 - 0.71; p &lt; 0.0001) and OS (HR: 0.52; 95% CI: 0.46 -0.59; p &lt; 0.0001). The 10-year OS rate was 79% / 64% for patients with continuous high / low adherence to endocrine therapy. Conclusions: As measured by the number of prescribed pills, adherence during the first 5 years of endocrine therapy was higher than expected by literature. Continuous adherence to ET over 5 years has a significant impact on OS and DRFS. Future research should focus on identifying factors that influence therapy adherence in HR+ EBC patients.
Long term survival in patients with bony oligometastatic breast cancer treated with curative intent: An institutional case series.
Authors: Alexandra Iancu, Shaveta Vinayak, William R Gwin, Hannah M. Linden, Jennifer M. Specht, Lynn Katherine Symonds, Nancy E. Davidson, Natasha Hunter
Journal: Journal of Clinical Oncology (2023)

e12574 Background: Despite recent advances in treatment, metastatic breast cancer is widely recognized as a generally incurable condition. However, oligometastatic disease remains a poorly characterized condition with few clinical trials exploring treatments and outcomes. The term itself lacks a formal definition but is often used to refer to breast cancer displaying ≤5 metastatic sites, not necessarily in the same organ. Surgical management of discrete metastases has failed to demonstrate long-term benefit, while radiotherapy for isolated bone metastases has shown promise in some retrospective studies resulting in prolonged disease-free interval. Metastatic breast tumors overexpressing HER2 represent a category where systemic therapy may offer some prolonged remission or even cure. Methods: We are conducting a retrospective review of breast cancer patients with oligometastatic disease, as defined by ≤5 sites of disease, treated at Fred Hutch Comprehensive Cancer Center (FHCC) from 2000 to 2022; we will characterize FHCC provider practices, therapies delivered, goals of treatment, and long-term outcomes. This larger ongoing effort will be reported in a separate publication. Among a cohort of patients initially identified and undergoing record review, we reviewed all patients with bone-only disease and report their outcomes here. Results: We initially identified 17 cases of oligometastatic breast cancer currently undergoing treatment at FHCC. Of these, we noted that five patients had bone-only metastases and displayed marked similarities in treatment and outcome. All presented with de novo metastatic disease, and all five had ≤2 sites of metastasis, all in the axial skeleton. Four had HER2+ tumors; of these, three were also hormone-receptor positive. The remaining patient had triple-negative disease. All were treated with curative intent, with radiation to isolated bone metastases delivered concurrently with adjuvant radiation to breast/axilla. All are living today, with a median 56 months of follow up. One remains on a systemic metastatic regimen with a CDK4/6 inhibitor, while the rest are off therapy or are completing a standard adjuvant regimen. Conclusions: Oligometastatic breast cancer represents a heterogeneous entity that may in some instances be curable, but we lack sufficient data to identify which patients may benefit from therapy with curative intent. Standard curative treatment combined with radiotherapy to isolated bone metastases produced long-term survival in five current FHCC patients, which is consistent with other reports on patients with a low burden of bone-dominant metastatic disease. Further research is needed to validate curative approaches to therapy for this understudied population.
Social determinants of health factors and palliative care services use among patients with metastatic breast cancer in Florida.
Authors: Fantine Giap, Young-Rock Hong, Julie Ann Bradley, Oluwadamilola Temilade Oladeru
Journal: Journal of Clinical Oncology (2023)

1102 Background: ASCO recommends palliative care (PC) as an adjunct to the oncologic standard of care for patients with metastatic cancer. However, current evidence on PC utilization in patients with breast cancer and its relationship with area-level social determinants of health (SDoH) factors is limited. Therefore, we examined the associations between county-level factors and PC utilization among patients with metastatic breast cancer (mBC) in Florida. Methods: We extracted patient-level data (n = 23,539 patients diagnosed with mBC between 2012 and 2021) from the OneFlorida+ Data Trust and linked it to county-level data (67 Florida counties) from the AHRQ-SDoH Database. PC utilization since cancer diagnosis was identified using ICD-9 code V66.7 or ICD-10 code Z51.5. We assessed differences in PC utilization with county-level SDoH factors (e.g., poverty rate, transportation resource, provider supply, racial segregation) using bivariate analysis. Multivariable Poisson regression, including significant factors from bivariate analysis, was used to compare the PC utilization for the SDoH factors. Results: Our study population's overall prevalence of PC utilization was 16.1%. PC utilization was higher for patients with mBC residing in counties with a higher proportion of residents living in poverty and with a greater supply of advanced practice providers (APP: NP, PA), general surgeons, and nursing homes. Patients with mBC in counties with higher proportions of residents who identified as immigrants, with limited English proficiency, without personal transportation, and having higher racial segregation had lower PC utilization. In adjusted analysis, the supply of APP (coefficient:0.12) and nursing homes (coefficient:0.09) was associated with increased PC utilization. Conversely, racial segregation (White vs. non-White) was associated with decreased PC utilization (coefficient: -0.07). Conclusions: PC utilization among patients with mBC was associated with several SDoH at the county level. Notably, low PC utilization was associated with racial residential segregation and fewer APPs and nursing homes. Further research is needed to identify mediators in these relationships to improve PC effectiveness for patients with mBC in Florida.
Is HER2 expression related to CDKi efficacy in HER2-negative luminal metastatic breast cancer?
Authors: María Yeray Rodríguez Garcés, Laura Fernández Madrigal, David Morales Pancorbo, Juan L. Bayo
Journal: Journal of Clinical Oncology (2023)

e13073 Background: Cyclin kinase inhibitors (CDKi) are the standard of care in the first line of luminal (Lum) metastatic breast cancer (MBC). HER2 overexpression is a classic risk factor in BC, however, the use of targeted therapy has changed the prognosis of this disease, even with anti-HER2 efficacy data in cases of low HER2 expression. We wonder if the level of HER2 expression can be a predictor of efficacy in treatment with CDKi. Methods: Descriptive, observational, retrospective and analytical study of patients with MBC treated with CDKi, in the period 2018-2022. Descriptive and analytical statistical analysis (IBM SPSS Statistics 22) using logistic regression and Kaplan-Meier with long-rank test to analyze the relationship between CKi efficacy and HER2 expression (negative = 0+; HER2 low = 1+ and 2 + with SISH negative). Results: We analyzed 152 patients (p) with Lum MBC under treatment with CDKi (median 58 years), in first and successive lines. HER2 expression: 31% 46p (0+), 54% 81p (1+) and 14% 21p (2+ and SISH negative). 41% were treated with palbociclib, 34% with ribociclib, and 26% with abemaciclib. Radiological response (RR) to CDKi was achieved by 34.1% (CRR 2.4%, PRR 31.7), and the rest stable disease (SD) or progressive disease (PD): SD 42% and PD 22%. In the overall OR, there was no evidence of a risk association between the response to CDKi and the level of HER2 expression. We obtained similar results in the analysis stratified by type of CDKi. In the multivariate study, for the variables CDKi type and HER2 expression, the logistic regression model was not statistically significant either. Regarding the Kaplan-Meier analysis, we compared the median PFS and OS using the Long-rank test, based on the expression of HER2. In the complete series we did not find statistically significant differences between the curves. In the palbociclib subgroup the curves split in favor of HER2 0+ vs. HER2 low: 44 months 95%CI (7.6-80) vs 16 months 95%CI (7.9-24); p = 0.01. Regarding OS, we found no significant differences. With ribociclib, the curves separate in favor of HER2 low versus HER2 0+: 33 months 95%CI (7.2-18) vs. 13 months 95%CI (23-42); p = 0.03. In OS we did not find significant differences either. In the subgroup with abemaciclib, we observed a trend towards greater survival in HER2 0+ patients, but with no significant difference between the PFS or OS curves. Conclusions: Based on our study, the expression of HER2 could be considered a predictor of efficacy depending on the CDKi used. We assume greater survival with palbociclib in HER2 negative patients (0+) and with ribociclib in HER2 low patients. We consider it essential to develop studies with a larger sample size and clinical trials that allow us to demonstrate the hypothesis of our work with scientific evidence.
A prospective real-world study to assess the effectiveness and safety of trastuzumab biosimilar in the adjuvant treatment of HER2-positive breast cancer: Preliminary safety results.
Authors: Ana Carolina Ferreira Cardoso, Debora De Melo Gagliato, Natália Mesquita Brito, Maura Gonzaga Lapa, Renata Virgínia Cavalcanti Santos, Erida Magaton, Vivienne Carduz Castilho
Journal: Journal of Clinical Oncology (2023)

e12532 Background: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) define a biosimilar as a biological molecule product that is highly similar to and has no clinically meaningful differences from an existing approved reference product. The trastuzumab biosimilar was the first oncology biosimilar approved in Brazil for HER2-positive breast cancer (BC) and advanced gastric cancer treatment. This study aimed to assess the effectiveness and safety of trastuzumab biosimilar (named as Zedora in Brazil) in the adjuvant setting among HER2-positive BC patients. Methods: This is a national, multicentric, observational, and prospective real-world study. Patients with early-stage HER2-positive BC who received at least one dose of trastuzumab biosimilar as adjuvant therapy were eligible. At the present date, 162 of 170 planned patients were recruited. Here, we present the preliminary safety data of the first 59 patients recruited in the study. The safety endpoint is the occurrence of adverse events (AEs), and the safety population included all patients who received at least one dose of trastuzumab biosimilar. We analyzed the AEs collected from the signature of the consent form until the end of adjuvant treatment. Results: Baseline patient characteristics among the 59 evaluated patients included a mean age of 51.7 ± 12.9 years, with 79.7% of them having a node-negative disease. Most patients had hormone-receptor-positive tumors (67.8% estrogen-receptor-positive and 55.9% progesterone-receptor-positive). The number of patients undergoing conservative surgery (67.8%) was higher than mastectomy (32.2%). The most frequent histological BC subtype was invasive ductal carcinoma (98.3%). All 59 participants received adjuvant anti-HER2 therapy, that included trastuzumab biosimilar administration trastuzumab biosimilar + pertuzumab (22.0%), and only two patients were receiving reference trastuzumab, which was switched to trastuzumab biosimilar upon entry into the study. The duration of adjuvant anti-HER2 therapy was 10.2 ± 2.2 months, ranging from 5.8 to 13.9 months. This time corresponds to, on average, 14 ± 3.2 cycles of 21 days. In total, 78.0% of the patients had at least one AE, four of them were serious AEs (6.8%), including three of severe intensity and one life-threatening. Table 1 lists the most reported AEs according to SOC (System Organ Class). Conclusions: The nature and severity of AEs observed to trastuzumab biosimilar were consistent with the known safety profile of trastuzumab. Clinical trial information: NCT03892655 . [Table: see text]
MRD assay to evaluate recurrence and response via a tumor-informed assessment: MARIA-Breast observational trial.
Authors: Edward D. Esplin, Kelli Swan, Lee Ifhar, Brandie Heald, Sarah M. Nielsen, Daniel Esteban Pineda Alvarez, William D. O'Callaghan, Robert Daber, Aadel A Chaudhuri
Journal: Journal of Clinical Oncology (2023)

TPS622 Background: The recognition that cancers release nucleic acids into the peripheral circulation of the patient has enabled a new paradigm for disease detection and surveillance. Detectable ctDNA in patients with solid tumors has been associated with disease prognosis pre-treatment, assessing response to therapy in the form of minimal residual disease (MRD), and monitoring for recurrence after curative intent treatment. Utilizing patient-specific genomic mutation profiling of an individual’s cancer from a tissue sample, in conjunction with the patient’s germline DNA, to create a personalized sequencing panel to then systematically analyze for a subset of these genetic mutations from ctDNA in blood is a strategy that has high sensitivity in detection of MRD. Studies have shown that pretreatment levels of ctDNA using this approach are a potential early indicator of disease recurrence after surgery, that ctDNA clearance may be an early predictor of favorable outcomes and have been shown to correlate with pathologic complete response (Forde et al. N Engl J Med. 2022, PMID:35403841), and that this approach has high sensitivity in its ability to detect recurrence for patients in advance of the current standard of care (Abbosh et al. Cancer Res (2020) 80 (16_Supplement): CT023). Methods: This is a multi-site, prospective, observational trial in the United States of 200 patients with early stage breast cancer undergoing curative intent treatment, who have FFPE tissue available from resection sufficient for a patient-specific bespoke MRD assay who are willing to provide serial whole blood specimens for ctDNA analysis. Participants are asked to provide study specimens prior to initial treatment intervention, after curative intent surgical resection, during adjuvant therapy (as applicable) and pre-recurrence follow-up. ctDNA will be analyzed with an NGS-based, tumor-informed MRD assay that identifies somatic mutations from DNA obtained from the patient’s tumor tissue, subtracts germline variants via NGS-based analysis of the patients germline DNA, and detects a selected set of between 18-50 tumor-specific ctDNA in their blood. All primary tumor specimens will undergo full exome sequencing using the Personalized Cancer Monitoring (PCM) assay. Impact of results of this CLIA-approved MRD assay on clinical decision making will be captured. The primary objective is to assess the ability of MRD to predict post-treatment recurrence. Further objectives are to correlate MRD status with pathologic complete response, determine the lead time to detection of recurrence compared to standard of care, and the association of MRD status with overall survival. Active enrollment started in March, 2022. Clinical trial information: NCT05219734 .